Acanthosis nigricans (AN), a skin disorder with high prevalence, represents a dermatological condition with esthetic implications, but otherwise mild symptoms. For any clinician, it is in fact the tip of the iceberg, leading him/her to investigate what lies beneath the surface, since AN points to a systemic problem or disease: metabolic disorder (most frequently), endocrine syndrome, medication side effects, malignancy, and genetic factors. Sometimes, it is the first observed sign of a malignancy or of diabetes mellitus, especially in patients with chronic metabolic disorder; therefore, it is not to be taken lightly. The present review summarizes the information in literature regarding the etiopathogenesis of AN. We propose a new classification that aims to better organize the different types of AN, with implications on the extent and urgency of the investigation plan, as well as various therapeutic algorithms. Therapy options are also presented, both systemic treatments that target the underlying disease, and local ones for esthetic reasons.